Venous Thromboembolism Flashcards
- What are the consequences of thromboembolism?
Death (5% mortality)
Recurrence
Thrombophlebitic syndrome (recurrent pain, swelling and ulcers)
Pulmonary hypertension
- What are the components of Virchow’s triad?
Blood composition (viscosity – haematocrit, protein/paraprotein)
Vessel wall
Blood flow
- List some anticoagulant molecules produced by the endothelium.
Thrombomodulin Endothelial protein C receptor Tissue factor pathway inhibitor Heparans NOTE: it does not normally produce tissue factor
- Which antiplatelet factors are produced by the endothelium?
NO
Prostacyclin
- Which stimuli can make the endothelium prothrombotic?
Infection, malignancy, vasculitis, trauma
- List the effects of infection/inflammation on the vessel wall.
Downregulation of anticoagulant molecules
Upregulation of adhesion molecules
TF may be expressed
Downregulation of prostacyclin production
- Describe the mechanism by which stasis promotes blood flow.
Leads to an accumulation of activated factors which promotes platelet adhesion and promotes leucocyte adhesion and transmigration
Hypoxia has an inflammatory effect on the endothelium
- List some causes of blood stasis.
Immobility (e.g. surgery)
Compression (e.g. tumour, pregnancy)
Viscosity (e.g. polycythaemia, paraprotein)
Congenital (e.g. vascular abnormalities)
- Which coagulation factor abnormality confers the highest risk of thrombosis?
Antithrombin deficiency
- Which drugs can be used to achieve immediate anticoagulation?
Heparin
Direct acting anti-Xa and anti-IIa
- List some types of heparin.
Low molecular weight heparin (SC)
Pentasaccharide (SC)
Unfractionated (IV)
- What is the mechanism of action of heparin?
Increases anticoagulant activity by potentiating anti-thrombin III
- List some disadvantages of heparin.
Administered by injection
Risk of osteoporosis
Variable renal dependence
- Name an anticoagulant that has a delayed effect.
Warfarin (2-3 days)
- How is LMWH monitored?
It has reliable pharmacokinetics so does not usually need monitoring
Anti-Xa assays can be used if renal failure or extremes or weight/risk
- How is unfractionated heparin monitored?
It has variable pharmacokinetics and a variable dose-response
Must be monitored with APTT or anti-Xa levels
- List some Anti-Xa DOACs.
Rivaroxaban
Apixaban
Edoxaban
- Name an Anti-IIa DOAC.
Dabigatran
- List some properties of DOACs.
Oral administration Immediate action (peak = 3-4 hours) Useful in long-term Short half-life No monitoring needed
- Outline the mechanism of action of warfarin.
It is a vitamin K epoxide reductase inhibitor meaning that it inhibits the gamma-carboxylation of factors 2, 7, 9 and 10
It also causes a reduction in protein C and protein S
- How can the action of warfarin be reversed?
Administering vitamin K – takes 12 hours
Giving factors 2, 7, 9 and 10 – immediate
- How is warfarin monitored?
Measuring INR
- Why is it difficult to control the effects of warfarin on INR?
Several variables that affect warfarin action including dietary vitamin K intake, variable absorption, interaction with other drugs and teratogenicity
- What is the antidote for heparin?
Protamine
